The Clock in Your Head

Genes running our body's clock operate in a coordinated way most of the time. But if they don't, depression can be the result.

When the brain's own biological clock keeps less than perfect time, clinical or major depression may be the result. This internal clock affects everything from mood, to eating behavior, to sleep patterns. So when it's running fast or slow, these basic processes are affected.

And the changes are happening at the level of a single gene.

Scientists have known for a long time about the subset of genes that regulates our circadian rhythms, the body’s internal clock. In normal healthy individuals, these genes turn on and off in a coordinated way throughout the day. These genes regulate, among other things, the body’s sleep-wake cycle and important daily and nightly functions like hunger, mental alertness, mood, and immunity.

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It was as if [the depressed individuals] were in a different time zone.

In people diagnosed with depression, the scientists discovered that the activity of these genes is out of phase with that of a normal individual, providing evidence that the body’s own internal clock is completely out of whack. Dysregulation of the body’s circadian rhythm has been implicated in chronic stress, one of the leading risk factors for clinical depression.

Up until now, it was extremely difficult to isolate and assay genetic material from the brain. Most autopsies come from death by natural causes, which can cause decay of certain genetic material.

In this study, the scientists used a clever trick. They screened over 12,000 genes from the brains of 55 different people who had died suddenly, such as from a heart attack or car accident. The rapid onset of death in these autopsies allowed the genetic material to be preserved, as if it were “frozen in time.”

The scientists were able to match the time of death to signs of genetic activity and identified hundreds of “clock” genes that followed a daily cycle in the brains of non-depressed patients who died suddenly. When they looked at those same genes in depressed patients, they found that far fewer genes followed a daily cycle, and those that did were out of phase with the genes in normal patients.

“It was as if [the depressed individuals] were in a different time zone, ” said Dr. Huda Akil one of the University of Michigan, Ann Arbor, researchers.

Akil hopes that the findings could lead to the development of new therapeutic drugs that would reset the biological clock in depressed subjects and possibly cure depression.

A shortcoming of the study is that the data did not include genetic information from the the part of the brain thought to be the “master clock,” the suprachiasmatic nucleus (SCN). The SCN resides deep in the brain and is torn away as the rest of the brain is dissected.

The next step for the scientists is to employ a method to study the brain’s “ clock ” genes without having to dissect it. Towards this goal, the researchers have already isolated blood and skin cells from the previously studied patients that they will attempt to generate into different brain cells in vitro. This method of testing will hopefully allow the researchers to identify the genetic signs of a disrupted clock without having to autopsy depressed subjects.

The study is published online in the Proceedings of the National Academy of Sciences.